Reference: Searle JS and Sanchez Y (2004) Stopped for repairs: a new role for nutrient sensing pathways? Cell Cycle 3(7):865-8

Abstract

In order to prevent division of damaged chromosomes, cells activate a checkpoint to inhibit mitotic progression in order to repair the damaged DNA. Upon detection of DNA damage two downstream checkpoint kinases, Chk1 and Rad53, are activated by the sensor kinase, Mec1, to block the metaphase to anaphase transition and mitotic exit, respectively. Recent data from studies with budding yeast suggested that the DNA damage checkpoint also enlists the cAMP dependent protein kinase (PKA) pathway, which is an integral part of the nutrient sensing mechanism in budding yeast, to inhibit mitosis in response to DNA damage. Genetic and biochemical evidence suggested that the PKA pathway contributes to the inhibition of mitotic progression by mediating the phosphorylation of the APC specificity factor Cdc20. Phosphorylation of Cdc20 assists the activity of the checkpoint pathways in the inhibition of the degradation of mitotic inhibitors securin, Pds1, and the B type cyclin, Clb2, in order to block anaphase and mitotic exit. Cdc20 was phosphorylated following DNA damage in a PKA and Mec1 dependent manner, suggesting PKA activation is dependent on Mec1. Here we discuss possible mechanisms for how PKA activity could be regulated in response to DNA damage and we will also address the implication of these results in evaluating current cancer treatments.

Interaction Annotations

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the
page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column
header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small
"i" buttons located within a cell for an annotation to view further details about experiment type and any other
genes involved in the interaction.

Gene Ontology Annotations

Increase the total number of rows showing on this page using the pull-down located below the table, or use the page
scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header
to sort by that column; filter the table using the "Filter" box at the top of the table.

Phenotype Annotations

Increase the total number of rows showing on this page using the pull-down located below the table, or use the page
scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header
to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i"
buttons located within a cell for an annotation to view further details.

Regulation Annotations

Increase the total number of rows displayed on this page using the pull-down located below the table, or use the
page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column
header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box
(for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to
further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, SPELL, or YeastMine.

Expression Datasets

Increase the total number of rows displayed on this page using the pull-down located below the table, or use the
page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column
header to sort by that column; filter the table using the "Filter" box at the top of the table; download this table
as a .txt file using the Download button;